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1. Tranexamic acid dose–response relationship for antifibrinolysis in postpartum haemorrhage during Caesarean delivery: TRACES, a double-blind, placebo-controlled, multicentre, dose-ranging biomarker study

Author

Anne-Sophie Ducloy-Bouthors, Sixtine Gilliot, Maeva Kyheng, David Faraoni, Alexandre Turbelin, Hawa Keita-Meyer, Agnès Rigouzzo, Gabriela Moyanotidou, Benjamin Constant, Francoise Broisin, Agnès L. Gouez, Rémi Favier, Edith Peynaud, Louise Ghesquiere, Gilles Lebuffe, Alain Duhamel, Delphine Allorge, Sophie Susen, Benjamin Hennart, Emmanuelle Jeanpierre, Pascal Odou, Cyril Huissoud, Charles Garabedian, Fanny Lassalle, Frederic J. Mercier, Catherine Barre-Drouard, Max Gonzalez Estevez, Julien Corouge, Anne-Sophie Baptiste, Anne-Frédérique Dalmas, Pierre Richart, Groupe de Recherche sur les formes Injectables et les Technologies Associées - ULR 7365 (GRITA), Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Hôpital Jeanne de Flandre [Lille], Service de Biostatistiques [CHRU Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Evaluation des technologies de santé et des pratiques médicales - ULR 2694 (METRICS), Hôpital Jeanne de Flandres, Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Toxicologie et Génopathies [CHRU Lille], Pôle de Biologie Pathologie Génétique [CHU Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Université de Lille, CHU Lille, Groupe de Recherche sur les formes Injectables et les Technologies Associées - ULR 7365 [GRITA], Evaluation des technologies de santé et des pratiques médicales - ULR 2694 [METRICS], Groupe de Recherche sur les formes Injectables et les Technologies Associées (GRITA) - ULR 7365, Récepteurs nucléaires, Maladies Cardiovasculaires et Diabète (EGID) - U1011, Centre Hospitalier Régional Universitaire [Lille] [CHRU Lille], and Récepteurs nucléaires, maladies cardiovasculaires et diabète - U 1011 [RNMCD]

Subjects
Anesthesiology and Pain Medicine, Tranexamic Acid, Double-Blind Method, Pregnancy, Cesarean Section, [SDV]Life Sciences [q-bio], Postpartum Hemorrhage, Humans, Female, Fibrinolysin, Blood Coagulation Disorders, Antifibrinolytic Agents, Biomarkers
Abstract

International audience; BackgroundThe optimal dose of tranexamic acid to inhibit hyperfibrinolysis in postpartum haemorrhage is unclear. Tranexamic Acid to Reduce Blood Loss in Hemorrhagic Cesarean Delivery (TRACES) was a double-blind, placebo-controlled, randomised, multicentre dose-ranging study to determine the dose–effect relationship for two regimens of intravenous tranexamic acid vs placebo.MethodsWomen experiencing postpartum haemorrhage during Caesarean delivery were randomised to receive placebo (n=60), tranexamic acid 0.5 g (n=57), or tranexamic acid 1 g i.v. (n=58). Biomarkers of fibrinolytic activation were assayed at five time points, with inhibition of hyperfibrinolysis defined as reductions in the increase over baseline in D-dimer and plasmin–antiplasmin levels and in the plasmin peak time.ResultsIn the placebo group, hyperfibrinolysis was evidenced by a mean increase over baseline [95% confidence interval] of 93% [68–118] for D-dimer level at 120 min and 56% [25–87] for the plasmin–antiplasmin level at 30 min. A dose of tranexamic acid 1 g was associated with smaller increases over baseline (D-dimers: 38% [13–63] [P=0.003 vs placebo]; plasmin–antiplasmin: –2% [–32 to 28] [P=0.009 vs placebo]). A dose of tranexamic acid 0.5 g was less potent, with non-significant reductions (D-dimers: 58% [32–84] [P=0.06 vs placebo]; plasmin–antiplasmin: 13% [18–43] [P=0.051]). Although both tranexamic acid doses reduced the plasmin peak, reduction in plasmin peak time was significant only for the 1 g dose of tranexamic acid.ConclusionsFibrinolytic activation was significantly inhibited by a dose of intravenous tranexamic acid 1 g but not 0.5 g. Pharmacokinetic–pharmacodynamic modelling of these data might identify the best pharmacodynamic monitoring criteria and the optimal tranexamic acid dosing regimen for treatment of postpartum haemorrhage.

Published
2022

2. Omicron Variant in the Critical Care Units of the Paris Metropolitan Area: The Reality Research Group

Author

Antoine Vieillard-Baron, Rémi Flicoteaux, Maud Salmona, Appoline Chariot, Bertrand De Maupeou D’Ableiges, Michael Darmon, Frédéric Batteux, Djillali Annane, Soufia Ayed, Elie Azoulay, Raphael Bellaiche, Sadek Beloucif, Enora Berti, Astrid Bertier, Sébastien Besset, Marlène Bret, Alain Cariou, Christophe Carpentier, Oussama Chaouch, Cyril Charron, Julien Charpentier, Cherifa Cheurfa, Bernard Cholley, Benjamin Chousterman, Sébastien Clerc, Yves Cohen, Alain Combes, Jean-Michel Constantin, Charles Damoisel, Vincent Degos, Sophie Demeret, Etienne De Montmollin, Alexandre Demoule, Francois Depret, Jean-Luc Diehl, Michel Djibré, Chung-Hi Do, Emmanuel Dudoignon, Jacques Duranteau, Muriel Fartoukh, Fabienne Fieux, Etienne Gayat, Mael Gennequin, Bertrand Guidet, Christophe Gutton, Sophie Hamada, Nicholas Heming, Romain Jouffroy, Hawa Keita-Meyer, Olivier Langeron, Brice Lortat-Jacob, Jonathan Marey, Alexandre Mebazaa, Bruno Megarbane, Armand Mekontso-Dessap, Jean-Paul Mira, Julie Molle, Nicolas Mongardon, Philippe Montravers, Capucine Morelot-Panzini, Safaa Nemlaghi, Bao-long Nguyen, Antoine Parrot, Romain Pasqualotto, Nicolas Peron, Lucile Picard, Marc Pineton de Chambrun, Benjamin Planquette, Benoit Plaud, Stéphanie Pons, Christophe Quesnel, Jean-Herlé Raphalen, Keyvan Razazi, Jean-Damien Ricard, Anne Roche, Benjamin Rohaut, Damien Roux, Laurent Savale, Jennifer Sobotka, Jean-Louis Teboul, Jean-François Timsit, Guillaume Voiriot, Emmanuel Weiss, Lucille Wildenberg, Elie Zogheib, and Bruno Riou

Subjects
Pulmonary and Respiratory Medicine, Intensive Care Units, Paris, Critical Care, Humans, Critical Care and Intensive Care Medicine
Published
2022

3. EPIDEMIOLOGICAL CHARACTERISTICS AND SEVERITY OF OMICRON VARIANT CASES IN THE APHP CRITICAL CARE UNITS

Author

Antoine Vieillard-Baron, Rémi Flicoteaux, Maud Salmona, Djillali Annane, Soufia Ayed, Elie Azoulay, Raphael Bellaiche, Sadek Beloucif, Enora Berti, Astrid Bertier, Sébastien Besset, Marlène Bret, Alain Cariou, Christophe Carpentier, Oussama Chaouch, Appoline Chariot, Cyril Charron, Julien Charpentier, Cherifa Cheurfa, Bernard Cholley, Sébastien Clerc, Alain Combes, Benjamin Chousterman, Yves Cohen, Jean-Michel Constantin, Charles Damoisel, Michael Darmon, Vincent Degos, Bertrand De Maupeou D’Ableiges, Sophie Demeret, Etienne De Montmollin, Alexandre Demoule, Francois Depret, Jean-Luc Diehl, Michel Djibré, Chung-Hi Do, Emmanuel Dudoignon, Jacques Duranteau, Muriel Fartoukh, Fabienne Fieux, Etienne Gayat, Mael Gennequin, Bertrand Guidet, Christophe Gutton, Sophie Hamada, Nicholas Heming, Romain Jouffroy, Hawa Keita-Meyer, Olivier Langeron, Brice Lortat-Jacob, Jonathan Marey, Alexandre Mebazaa, Bruno Megarbane, Armand Mekontso-Dessap, Jean-Paul Mira, Julie Molle, Nicolas Mongardon, Philippe Montravers, Capucine Morelot-Panzini, Safaa Nemlaghi, Bao-long Nguyen, Antoine Parrot, Romain Pasqualotto, Nicolas Peron, Lucile Picard, Marc Pineton de Chambrun, Benjamin Planquette, Benoit Plaud, Stéphanie Pons, Christophe Quesnel, Jean-Herlé Raphalen, Keyvan Razazi, Jean-Damien Ricard, Anne Roche, Benjamin Rohaut, Damien Roux, Laurent Savale, Jennifer Sobotka, Jean-Louis Teboul, Jean-François Timsit, Guillaume Voiriot, Emmanuel Weiss, Lucille Wildenberg, Elie Zogheib, Bruno Riou, and Frédéric Batteux

Abstract

ImportanceInformation about the severity of Omicron is scarce.ObjectiveTo report the respective risk of ICU admission in patients hospitalized with Delta and Omicron variants and to compare the characteristics and disease severity of critically ill patients infected with both variants according to vaccination status.DesignAnalysis from the APHP database, called Reality, prospectively recording the following information in consecutive patients admitted in the ICU for COVID-19: age, sex, immunosuppression, vaccination, pneumonia, need for invasive mechanical ventilation, time between symptom onset and ICU admission, and in-ICU mortality. Retrospective analysis on an administrative database, “Système d’Information pour le Suivi des Victimes” (SI-VIC), which lists hospitalized COVID-19 patients.Setting39 hospitals in the Paris area from APHP group.ParticipantsPatients hospitalized from December 1, 2021 to January 18, 2022 for COVID-19.Main outcomes and measuresRisk of ICU admission was evaluated in 3761 patients and Omicron cases were compared to Delta cases in the ICU in 888 consecutive patients.ResultsOn January 18, 45% of patients in the ICU and 63.8% of patients in conventional hospital units were infected with the Omicron variant (p < 0.001). The risk of ICU admission with Omicron was reduced by 64% than with Delta (9.3% versus 25.8% of cases, respectively, p < 0.001). In critically ill patients, 400 had the Delta variant, 229 the Omicron variant, 98 had an uninformative variant screening test and 161 did not have information on variant screening test. 747 patients (84.1%) were admitted for pneumonia. Compared to patients infected with Delta, Omicron patients were more vaccinated (pConclusion and relevanceCompared to the Delta variant, the Omicron variant is less likely to result in ICU admission and less likely to be associated with pneumonia. However, when patients with the Omicron variant are admitted for pneumonia, the severity seems similar to that of patients with the Delta variant, with more immunocompromised and vaccinated patients and no difference in adjusted in-ICU mortality. Further studies are needed to confirm our results.

Published
2022

4. Epidemiological Characterisation of Omicron Variant Cases in the APHP Critical Care Units

Author

Antoine Vieillard-Baron, Remi Flicoteaux, Maud Salmona, djillali annane, Soufia Ayed, Elie Azoulay, Raphael Bellaiche, Sadek Beloucif, Enora Berti, Astrid Bertier, Sebastien Besset, Marlène Bret, Alain Cariou, Christophe Carpentier, Oussama Chaouch, Cyril Charron, Julien Charpentier, Cherifa Cheurfa, Bernard Cholley, Sebastien Clerc, Alain Combes, Benjamin Chousterman, Yves Cohen, Jean Michel Constantin, Charles Damoisel, Michael Darmon, Vincent Degos, Bertrand De Maupeou D'Ableiges, Sophie Demeret, Etienne De Montmollin, Alexandre Demoule, François depret, Jean-Luc Diehl, Michel Djibré, Do Chung-Hi, Emmanuel Dudoignon, Jacques Duranteau, Muriel Fartoukh, Fabienne Fieux, Etienne Gayat, Mael Gennequin, Bertrand Guidet, Christophe Gutton, Sophie HAMADA, Nicholas Heming, Romain Jouffroy, Hawa Keita-Meyer, Olivier Langeron, Brice Lortat-Jacob, Jonathan Marey, Alexandre Mebazaa, Bruno Megarbane, Armand Mekontso Dessap, Jean-Paul Mira, Julie Molle, Philippe Montravers, Capucine Morelot-Panzini, Safaa Nemlaghi, Bao-long Nguyen, Antoine Parrot, Romain Pasqualotto, Nicolas Peron, Lucile Picard, marc Pineton de Chambrun, Benjamin Planquette, Benoit Plaud, Pons Stephanie, Christophe Quesnel, Jean-Herle Raphalen, Keyvan Razazi, Jean-Damien Ricard, Anne Roche, Benjamin Rohaut, Damien Roux, Laurent Savale, Jennifer Sobotka, Jean-Louis Teboul, Jean-Francois Timsit, Guillaume Voiriot, Emmanuel Weiss, Lucille Wildenberg, Elie Zogheib, Bruno Riou, and Frederic Batteux

Published
2022

5. Normal delivery: physiologic support and medical interventions. Guidelines of the French National Authority for Health (HAS) with the collaboration of the French College of Gynecologists and Obstetricians (CNGOF) and the French College of Midwives (CNSF)

Author

Karine Petitprez, Aurélien Mattuizzi, Sophie Guillaume, Maud Arnal, France Artzner, Catherine Bernard, François-Marie Caron, Isabelle Chevalier, Claude Daussy-Urvoy, Anne-Sophie Ducloy-Bouthorsc, Jean-Michel Garnier, Hawa Keita-Meyer, Jacqueline Lavillonnière, Valérie Lejeune-Sadaa, Camille Le Ray, Anne Morandeau, Marjan Nadjafizade, Franck Pizzagalli, Clemence Schantz, Thomas Schmitz, Raha Shojai, Bernard Hédon, and Loïc Sentilhes

Subjects
medicine.medical_specialty, Psychological intervention, Oxytocin, National authority, 03 medical and health sciences, 0302 clinical medicine, Pregnancy, Active phase, medicine, Humans, Cardiotocography, Stage (cooking), Intermittent Auscultation, 030219 obstetrics & reproductive medicine, medicine.diagnostic_test, Obstetrics, business.industry, Normal delivery, Infant, Newborn, Obstetrics and Gynecology, Delivery, Obstetric, 030220 oncology & carcinogenesis, Pediatrics, Perinatology and Child Health, Female, business, Umbilical cord clamping
Abstract

Objective To define for women at low obstetric risk methods of management that respect the rhythm and the spontaneous course of giving birth as well as each woman's preferences. Methods These clinical practice guidelines were developed through professional consensus based on an analysis of the literature and of the French and international guidelines available on this topic. Results Labor should be monitored with a partograph (professional consensus). Digital cervical examination should be offered every 4 h during the first stage of labor, hourly during the second. The choice between continuous (cardiotocography) or discontinuous (by cardiotocography or intermittent auscultation) monitoring should be left to the woman (professional consensus). In the active phase of the first stage of labor, dilation speed is considered abnormal if it is less than 1 cm/4 h between 5 and 7 cm or less than 1 cm/2 h after 7 cm. In those cases, an amniotomy is recommended if the membranes are intact, and the administration of oxytocin if the membranes are already broken and uterine contractions are judged insufficient (professional consensus). It is recommended that pushing not begin when full dilation has been reached; rather, the fetus should be allowed to descend (grade A). Umbilical cord clamping should be delayed beyond the first 30 s in newborns who do not require resuscitation (grade C). Conclusion The establishment of these clinical practice guidelines should enable women at low obstetric risk to receive better care in conditions of optimal safety while supporting physiologic birth.

Published
2021

6. Spinal anesthesia for Cesarean delivery in women with COVID-19 infection: questions regarding the cause of hypotension

Author

Dominique Chassard, Hawa Keita Meyer, Estelle Morau, Dan Benhamou, and Frédéric J. Mercier

Subjects
medicine.medical_specialty, 2019-20 coronavirus outbreak, Coronavirus disease 2019 (COVID-19), Pneumonia, Viral, Anesthesia, Spinal, Betacoronavirus, Pregnancy, Anesthesiology, medicine, Humans, Cesarean delivery, Pandemics, Anesthetics, SARS-CoV-2, business.industry, COVID-19, Spinal anesthesia, General Medicine, medicine.disease, Pneumonia, Anesthesiology and Pain Medicine, Anesthesia, Female, Hypotension, Coronavirus Infections, business
Published
2020

7. An IgG-induced neutrophil activation pathway contributes to human drug-induced anaphylaxis

Author

Friederike Jönsson, Caroline Sauvan, Florence Tubach, Skander Necib, Catherine Paugam-Burtz, Qianqian Zhu, Christelle Ganneau, Vanessa Granger, Bernard Cholley, Hawa Keita-Meyer, Marc Fischler, Philippe Montravers, Dan Longrois, Laurent Jacob, Matthieu Le Dorze, C. Neukirch, Pascale Nicaise-Roland, Sylvie Chollet-Martin, Olivier Langeron, Caitlin M. Gillis, Pierre Bruhns, Sylvie Bay, Luc de Chaisemartin, Aurélie Gouel-Chéron, Michel Aubier, Benoit Plaud, Maria Hurtado-Nedelec, Marie-Thérèse Guinnepain, Fadia Dib, Jönsson, Friederike, Role of myeloid cells, their mediators and their antibody receptors in allergic shock (anaphylaxis) using humanized mouse models and clinical samples - MYELOSHOCK - - EC:FP7:ERC2014-09-01 - 2019-08-31 - 616050 - VALID, Anticorps en thérapie et pathologie - Antibodies in Therapy and Pathology, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Inflammation, Chimiokines et Immunopathologie [Châtenay-Malabry], Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Chimie des Biomolécules - Chemistry of Biomolecules, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Hôpital Beaujon, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Hôpital Beaujon [AP-HP], Université Paris Diderot - Paris 7 (UPD7), Hôpital Louis Mourier - AP-HP [Colombes], Recherche Clinique ville-hôpital, Méthodologies et Société (REMES), Hôpital Lariboisière-Fernand-Widal [APHP], Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Histopathologie humaine et Modèles animaux, Institut Pasteur [Paris] (IP), Hôpital Saint-Louis, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Hôpital Foch [Suresnes], Lab Excellence Inflamex, Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), The NASA study was funded by AP-HP (Direction de la Recherche Clinique et de l’Innovation) through a 'Contrat de Recherche Clinique 2011' to S.C.-M. by INSERM and the French Ministry of Health (Direction Générale de l’Offre de Soin, Paris, France) through a 'Recherche Clinique translationnelle 2012' grant to P.B., by the European Research Council (ERC)–Seventh Framework Program (ERC-2013-CoG 616050) to P.B., by the Institut Pasteur, and by the INSERM. A.G.-C. benefited from a stipend provided by AP-HP, Paris, France and by the Institut Pasteur, Paris, France and from a grant provided by INSERM, SFAR (Société Française d’Anesthésie et de Réanimation), and SRLF (Société de Réanimation de Langue Française) through the 'Bourse de Recherche du Comité d’interface INSERM-SFAR-SRLF 2012.' C.M.G. was supported partly by a stipend from the Pasteur-Paris University (PPU) International PhD program and by the Institut Carnot Pasteur Maladies Infectieuses. P.B. benefited from an additional support from AP-HP through a 'Contral Local d’Interface 2014' and the 'Département Hospitalo-Universitaire' (DHU) FIRE. The sponsor of the NASA study was the Direction de la Recherche Clinique et de l’Innovation de l’AP-HP (France). F.J. is an employee of the CNRS., We are thankful to the team of the Pharmacoepidemiology Center of the Assistance Publique-Hôpitaux de Paris (AP-HP) and, in particular, N. Yelles, K. Chandirakumaran, and I. Younes at the Bichat Hospital for help with the NASA study logistics. We thank all clinicians from the NASA study group for help with patient recruitment, in particular, V. Faitot, A. Mebazaa, J. Mantz (deceased), S. Roche, C. Chahine, J. Bresson, and A. Mignon. From the Institut Pasteur, Paris, France, we thank B. Iannascoli for help with antibody purification, D. A. Mancardi for flow cytometry setups, F. Bonhomme for mass and nuclear magnetic resonance analyses of carboxylated rocuronium and suxamethonium, and B. Baron and P. England for MST. We thank V. Guérineau (Institut de Chimie des Substances Naturelles, Gif-sur-Yvette, France) for the mass analyses of bioconjugates and M. Parent, S. Peltier, L. Gaillanne, and C. S. Louis-Augustin (Immunology Laboratory, Bichat Hospital, Paris) for help with sample management and immunology diagnostic tests. We thank M. Pallardy (Toxicology department, UFR de Pharmacie de l’Université Paris-Sud and INSERM UMR996) for discussions on NMBA allergy., European Project: 616050,EC:FP7:ERC,ERC-2013-CoG,MYELOSHOCK(2014), Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris], Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Institut Pasteur [Paris], and Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
Adult, Male, 0301 basic medicine, Down-Regulation, Immunoglobulin E, medicine.disease_cause, Severity of Illness Index, Neutrophil Activation, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Allergen, Antibody Specificity, medicine, Humans, Myeloid Cells, Platelet Activating Factor, [SDV.IMM.ALL]Life Sciences [q-bio]/Immunology/Allergology, Receptor, Anaphylaxis, Aged, biology, business.industry, Receptors, IgG, Degranulation, General Medicine, Middle Aged, medicine.disease, 3. Good health, Hypersensitivity reaction, 030104 developmental biology, chemistry, Immunoglobulin G, Immunology, biology.protein, Female, Neuromuscular Blocking Agents, Antibody, business, Biomarkers, Histamine, [SDV.IMM.ALL] Life Sciences [q-bio]/Immunology/Allergology, 030215 immunology
Abstract

International audience; Anaphylaxis is a systemic acute hypersensitivity reaction that is considered to depend on allergen-specific immunoglobulin E (IgE) antibodies and histamine release by mast cells and basophils. Nevertheless, allergen-specific IgG antibodies have been proposed to contribute when the allergen is an abundant circulating large molecule, e.g., after infusions of therapeutic antibodies or dextran. Data from animal models demonstrate a pathway involving platelet-activating factor (PAF) release by monocytes/macrophages and neutrophils activated via their Fc gamma receptors (FcγRs). We hypothesized that such a pathway may also apply to small drugs and could be responsible for non-IgE-mediated anaphylaxis and influence anaphylaxis severity in humans. We prospectively conducted a multicentric study of 86 patients with suspected anaphylaxis to neuromuscular-blocking agents (NMBAs) during general anesthesia and 86 matched controls. We found that concentrations of anti-NMBA IgG and markers of FcγR activation, PAF release, and neutrophil activation correlated with anaphylaxis severity. Neutrophils underwent degranulation and NETosis early after anaphylaxis onset, and plasma-purified anti-NMBA IgG triggered neutrophil activation ex vivo in the presence of NMBA. Neutrophil activation could also be observed in patients lacking evidence of classical IgE-dependent anaphylaxis. This study supports the existence of an IgG-neutrophil pathway in human NMBA-induced anaphylaxis, which may aggravate anaphylaxis in combination with the IgE pathway or underlie anaphylaxis in the absence of specific IgE. These results reconcile clinical and experimental data on the role of antibody classes in anaphylaxis and could inform diagnostic approaches to NMBA-induced acute hypersensitivity reactions.

Published
2019

9. Douleur obstétricale : l’échelle visuelle analogique et échelle numérique sont corrélées mais l’échelle numérique a une meilleure capacité à déterminer un soulagement après analgésie péridurale

Author

Emilie Berthe, Hawa Keita-Meyer, Smail Ghanem, Sophie Nebout, and David Hajage

Subjects
Anesthesiology and Pain Medicine
Abstract

Introduction Hors contexte obstetricale, il a ete demontre que l’echelle visuelle analogique (EVA) et l’echelle numerique (EN) etaient correlees mais que cette correlation etait plus forte pour les scores de douleur bas par rapport aux scores plus eleves [1] . Il a egalement ete decrit une difference entre ces 2 echelles dans leur capacite a detecter un soulagement de la douleur apres traitement [1] . Nous avons mene une etude sur la douleur obstetricale pour determiner la correlation et le degre d’agrement entre l’EVA et l’EN, ainsi que la sensibilite de ces 2 echelles a detecter un soulagement apres l’APD. Patientes et methodes Etude prospective observationnelle menee sur une periode d’un mois dans une maternite de type 3. Les patientes en travail desireuses d’une APD ont ete incluses. Avant et 30 min apres la pose de l’APD, les parturientes ont eu une evaluation par EVA et EN au pic des contractions uterines. De plus, 30 min apres l’APD, elles indiquaient leur niveau de soulagement en donnant le % de reduction de la douleur. Pour l’EVA et l’EN, le % de reduction de la douleur etait calcule : 100 × ([score avant APD − score apres APD]/score avant APD). Les donnees demographiques et obstetricales ont ete recueillies. Analyse statistique par coefficient de concordance de correlation (CCC) et graphique de Bland et Altman avec limites d’agrement (1,96 × ecart-type [ET]). Resultats Trente et un patientes ont ete incluses. Leurs caracteristiques figurent dans le Tableau 1 . Les scores de douleur avant APD etaient a 7,3 ± 1,9 et 7,7 ± 1,9, respectivement pour l’EVA et l’EN. Trente min apres, l’EVA etait a 0,8 ± 1,5 et l’EN a 1,4 ± 1,8. Le CCC (IC95 %) entre l’EVA et l’EN etait a 0,86 (0,73–0,92) et 0,90 (0,82–0,95) respectivement avant et 30 min apres l’APD. Le CCC (IC95 %) entre le % de reduction de la douleur declaree par la patiente et celle calculee pour l’EVA et l’EN etait respectivement de 0,72 (0,51–0,85) et 0,80 (0,63–0,90). Les analyses de BA avant et apres APD sont representees par les Fig. 1 , Fig. 2 . Le biais (limites d’agrement) entre % de reduction de la douleur declaree et celui calcule pour l’EVA et l’EN etait respectivement de −8,9 (34,5) et −3,2 (30). Discussion Cette etude montre une forte correlation entre EVA et EN aussi bien pour les douleurs fortes que pour les douleurs faibles apres APD. Le biais est faible entre l’EVA et l’EN que ce soit avant ou apres APD puisque la difference moyenne est proche de 0 (−0,4 et −0,5) avec une dispersion moins importante pour les douleurs les plus faibles. Les 2 echelles ont une sensibilite a detecter un soulagement moyennement correlee a la reduction de la douleur declaree par les patientes. Neanmoins, l’EN a la meilleure concordance avec le biais le plus faible et la dispersion la moins importante. L’EN permet donc de mieux apprehender l’efficacite analgesique de l’APD. Si ces resultats sont confirmes, cette echelle pourrait etre celle a privilegier pour les etudes cliniques.

Published
2015

10. Intérêt de la simulation pour l’apprentissage de la pose de l’analgésie péridurale (APD) obstétricale : étude comparative sur des internes en anesthésie-réanimation (DESAR)

Author

Florian Deleu, Harold Bonvallot, Emilie Charbit, Arselen Ghribi, Antoine Mortazavi, Hawa Keita-Meyer, Hugo Flis-Richard, and Sophie Nebout

Subjects
Anesthesiology and Pain Medicine
Abstract

Introduction L’enseignement par simulation est une opportunite pour former les etudiants aux gestes techniques difficiles et/ou a risque et ainsi ameliorer la securite des patients [1] . La pose d’une analgesie peridurale (APD) fait partie de ces gestes. Le but de notre etude etait d’apprecier l’impact d’une formation par simulation sur mannequin des internes (DESAR) debutants sur la pose de l’APD en contexte obstetrical. Materiel et methodes Etude observationnelle de type avant–apres dans un centre universitaire avec une maternite de type III, menee sur des DESAR 1 er semestre au tout debut de leur stage. Deux groupes ont ete compares sur 2 periodes : groupe 1 (2010, n = 3) et groupe 2 (2014, n = 5). Les 2 groupes ont recu la 1 re semaine de stage un enseignement theorique sur l’APD. Le groupe 2 a en plus beneficie d’une seance de simulation sur un mannequin rachis adapte a l’apprentissage de l’APD (Lumbar Epidural Injection Trainer - EIT 100 - Pharmabotics Ltd). Sur chacune des periodes, les DESAR beneficiaient d’un compagnonnage par un senior pour les premieres poses d’APD. Le materiel utilise et les protocoles d’analgesie n’ont pas ete modifies entre les 2 periodes. Les parametres recueillis a partir du dossier et de l’interrogatoire des patientes etaient : nombre d’APD posee par un senior dans un 2 nd temps, nombre de ponctions necessaire pour la pose de l’APD, presence de paresthesies a la pose, ponction durale, presence d’une douleur au point de ponction a j1–j2 et son score de douleur evalue par echelle numerique (EN, 0 a 10). Statistique par test de Chi 2 et test- t de Student, significativite pour un p Resultats Soixante-huit poses d’APD ont ete evaluees pour le groupe 1 contre 60 pour le groupe 2. Les resultats figurent dans le Tableau 1 . Les donnees sont exprimees en n (%). Les scores de douleur au point de ponction etaient de 4,8 ± 1,7 et 3 ± 1,7 ( p = 0,001), respectivement pour le groupes 1 et 2. Discussion Associe a un enseignement theorique et a un compagnonnage, l’apprentissage de la pose de l’APD par simulation, de jeunes DESAR, permet d’ameliorer la realisation de ce geste sur certains aspects et ainsi le confort des patientes. Il limite les desagrements comme les paresthesies lors de la pose de l’APD, la frequence et l’intensite des douleurs au point de ponction dans les 1 er jours post-partum. Ces resultats devront etre confirmes sur des series plus importantes d’internes.

Published
2015

11. Comparaison des performances du TOF Watch et du TOF Scan pour évaluation la curarisation résiduelle chez des patients obèses morbides

Author

Marylin Smeyers, Catherine Fournier, David Hajage, Gilles Rubéo-Lisa, Hawa Keita-Meyer, Manuel Sukami, and Arselen Ghribi

Subjects
Anesthesiology and Pain Medicine
Abstract

Introduction La curarisation residuelle est definie par la presence d’une valeur du train de quatre (TdQ) mesure a l’adducteur du pouce inferieure a 90 %. Elle induit des effets deleteres bien identifies, source d’une majoration de la morbidite et de la mortalite perioperatoire en l’absence d’une antagonisation pharmacologique [1] . Les patients obeses morbides sont une population particulierement a risque de complications respiratoires en cas de curarisation residuelle. Le but de notre etude etait de comparer les performances de 2 moniteurs de la curarisation, l’un necessitant un calibrage, le TOF Watch® et l’autre non calibre le TOF Scan®, pour estimer le niveau de curarisation residuelle chez des patients obeses morbides. Materiel et methodes Etude pilote prospective observationnelle, menee entre janvier et fevrier 2015 dans un centre universitaire. Les patients inclus beneficiaient d’une chirurgie bariatrique (by-pass, sleeve gastrectomie) par voie laparoscopique sous anesthesie generale avec intubation oro-tracheale et curarisation pour l’intubation (succynilcholine ou atracurium) et la chirurgie (atracurium). Les donnees recueillies etaient demographiques, chirurgicales, anesthesiques ainsi que les donnees de la curarisation residuelle. Celle-ci etait evaluee des l’obtention de 4 reponses au TdQ par le rapport T4/T1 affiche. La concordance entre les 2 appareils a ete analysee par le coefficient de concordance de correlation (CCC) et un graphique de Bland et Altman avec limites d’agrement (1,96 X ecart-type [ET]). Resultats Vingt et un patients ont ete inclus dans l’etude. Les caracteristiques de la population sont presentees dans le Tableau 1 . La comparaison des performances des 2 moniteurs pour l’evaluation de la curarisation residuelle a pu etre faite pour 12 patients. Le CCC (95 % IC) des rapports T4/T1 etait de 0,32 (0,12–0,71). La concordance par graphique de BA est presentee dans la Fig. 1 . Le rapport T4/T1 n’etait pas significativement different (biais a -6,25 %) mais avec une large dispersion (limites d’agrement a ± 65,7 %). Discussion Cette etude preliminaire menee sur des patients obeses morbides, montre qu’apres curarisation par atracurium, il existe une mauvaise concordance entre le TOF Watch® et le TOF Scan® pour l’estimation de la curarisation residuelle. Cette variabilite peut influencer de facon plus ou moins appropriee la decision de decurarisation chez cette population a risque. L’absence de biais significatif est en accord avec la litterature dans d’autres contextes [2] . Cependant, l’importance de la dispersion necessite des etudes avec des collectifs plus importants pour valider ce resultat et en determiner les raisons.

Published
2015

12. High-dose tranexamic acid reduces blood loss in postpartum haemorrhage

Author

Anne-Sophie Ducloy-Bouthors, Laurent Mandelbrot, Hawa Keita-Meyer, Sandrine Depret-Mosser, Cyril Huissoud, Brigitte Jude, Nadia Tillouche, Sophie Susen, Sylvie Fontaine, Françoise Le Goueff, Benoit Vallet, F. Broisin, and Alain Duhamel

Subjects
Adult, 030204 cardiovascular system & hematology, Critical Care and Intensive Care Medicine, Loading dose, law.invention, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Randomized controlled trial, law, Pregnancy, Antifibrinolytic agent, medicine, Humans, 030212 general & internal medicine, Prospective Studies, Prospective cohort study, Dose-Response Relationship, Drug, Vaginal delivery, business.industry, Research, Postpartum Hemorrhage, medicine.disease, Antifibrinolytic Agents, 3. Good health, Treatment Outcome, Tranexamic Acid, Anesthesia, Injections, Intravenous, Female, Packed red blood cells, business, Tranexamic acid, medicine.drug
Abstract

Introduction Our purpose in conducting this study was to determine whether administration of high-dose tranexamic acid (TA) at the time of diagnosis of postpartum haemorrhage (PPH) could reduce blood loss. Methods This was a randomised, controlled, multicentred, open-label trial. Women with PPH >800 mL following vaginal delivery were randomly assigned to receive TA (loading dose 4 g over 1 hour, then infusion of 1 g/hour over 6 hours) or not. In both groups, packed red blood cells (PRBCs) and colloids could be used according to French guidelines. The use of additional procoagulant treatments was permitted only in cases involving intractable bleeding. The primary objective was to assess the efficacy of TA in the reduction of blood loss in women with PPH, and the secondary objectives were the effect of TA on PPH duration, anaemia, transfusion and the need for invasive procedures. Results A total of 144 women fully completed the protocol (72 in each group). Blood loss between enrolment and 6 hours later was significantly lower in the TA group than in the control group (median, 173 mL; first to third quartiles, 59 to 377) than in controls (221 mL; first to third quartiles 105 to 564) (P = 0.041). In the TA group, bleeding duration was shorter and progression to severe PPH and PRBC transfusion was less frequent than in controls (P < 0.03). Invasive procedures were performed in four women in the TA group and in seven controls (P = NS). PPH stopped after only uterotonics and PRBC transfusion in 93% of women in the TA group versus 79% of controls (P = 0.016). Mild, transient adverse manifestations occurred more often in the TA group than in the control group (P = 0.03). Conclusions This study is the first to demonstrate that high-dose TA can reduce blood loss and maternal morbidity in women with PPH. Although the study was not adequately powered to address safety issues, the observed side effects were mild and transient. A larger international study is needed to investigate whether TA can decrease the need for invasive procedures and reduce maternal morbidity in women with PPH. Trial registration Controlled Trials ISRCTN09968140.

Published
2011

13. Low end-tidal CO2 as a real-time severity marker of intra-anaesthetic acute hypersensitivity reactions

Author

L. de Chaisemartin, Pascale Nicaise-Roland, A. Sabahov, Aurélie Gouel-Chéron, Friederike Jönsson, Pierre Bruhns, Sylvie Chollet-Martin, M-T Guinnepain, C. Neukirch, Dan Longrois, Vanessa Granger, Anticorps en thérapie et pathologie - Antibodies in Therapy and Pathology, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'anesthésie - réanimation chirurgicale [CHU Bichat], Université Paris Diderot - Paris 7 (UPD7)-AP-HP - Hôpital Bichat - Claude Bernard [Paris]-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Laboratoire d'Immunologie 'Autoimmunité et Hypersensibilités' [AP-HP Hôpital Bichat, Paris], AP-HP - Hôpital Bichat - Claude Bernard [Paris], Inflammation, Chimiokines et Immunopathologie [Châtenay-Malabry], Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Hôpital Foch [Suresnes], Service de Pneumologie [Bichat], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris]-Université Paris Diderot - Paris 7 (UPD7)-Centre de Compétence pour les Maladies Pulmonaires Rares, Physiopathologie et Epidémiologie des Maladies Respiratoires (PHERE (UMR_S_1152 / U1152)), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), The NASA study was financed by AP-HP through a « Contrat de Recherche Clinique 2011 », by INSERM (Institut National de la Santé et de la Recherche Médicale) and by DGOS (Direction Générale de l’Offre de Soins, Paris, France) through a « Recherche Clinique translationnelle 2012» grant. A.G.-C. benefited from a stipend provided by AP-HP, Paris, France and by the Institut Pasteur, Paris, France. F.J. is an employee of the Centre National de la Recherche Scientifique (CNRS). P.B. benefited from an additional support from AP-HP through a 'Contral Local d’Interface 2014' and the 'Département Hospitalo-Universitaire' (DHU) FIRE., NASA study group : Philippe Montravers MD PhD(1), Caitlin M. Gillis PhD(2), David A. Mancardi PhD(2), Michel Aubier MD PhD(3,4), Caroline Sauvan MD(4), Marc Fischler MD PhD(5), Julie Bresson MD(5), Catherine Paugam-Burtz MD PhD(6), Skander Necib MD(6), Alexandre Mebazaa MD PhD(7), Matthieu Le Dorze MD(7), Laurent Jacob MD PhD(8), Carole Chahine MD(8), Hawa Keita-Meyer MD PhD(9), Valentina Faitot MD(9), Olivier Langeron MD PhD(10), Sabrine Roche MD(10), Bernard Cholley MD PhD(11) and Jean Mantz MD Ph(D11),* - *Deceased (1) Département d'anesthésie-réanimation, Hôpital Bichat, AP-HP, Paris, France, (2) Unit of Antibodies in Therapy & Pathology, INSERM U1222, Institut Pasteur, Paris, France, (3) INSERM U1152, Universite Paris Diderot Paris 7, Paris, France, (4) Service de pneumologie et d'allergologie, Hôpital Bichat, AP-HP, DHU FIRE, Paris, France, (5) Département d'anesthésie-réanimation, Hôpital Foch, Suresnes, France, (6) Département d'anesthésie-réanimation, Hôpital Beaujon, AP-HP, Clichy, France, (7) Département d'anesthésie-réanimation, Hôpital Lariboisière, AP-HP, Paris, France, (8) Département d'anesthésie-réanimation, Hôpital Saint Louis, AP-HP, Paris, France, (9) Département d'anesthésie-réanimation, Hôpital Louis Mourier, AP-HP, Colombes, France, (10) Département d'anesthésie-réanimation, Hôpital Pitié Salpêtrière, AP-HP, Paris, France, and (11) Département d'anesthésie-réanimation, Hôpital Européen Georges Pompidou, AP-HP, Paris, France, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Centre de Compétence pour les Maladies Pulmonaires Rares, Martin, Marie, Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)

Subjects
Male, Severity of Illness Index, Hypoxemia, MESH: Aged, 80 and over, 0302 clinical medicine, Hypocapnia, 030202 anesthesiology, Anesthesia, Young adult, Intraoperative Complications, neuromuscular blocking agents, Aged, 80 and over, MESH: Aged, MESH: Middle Aged, MESH: Carbon Dioxide/metabolism, anaesthesia, Middle Aged, MESH: Intraoperative Complications/diagnosis, respiratory system, 3. Good health, MESH: Reproducibility of Results, Epinephrine, MESH: Young Adult, Acute Disease, MESH: Acute Disease, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, medicine.symptom, Anaphylaxis, medicine.drug, Adult, medicine.medical_specialty, Adolescent, [SDV.IMM] Life Sciences [q-bio]/Immunology, MESH: Intraoperative Complications/metabolism, Drug Hypersensitivity, Young Adult, 03 medical and health sciences, MESH: Severity of Illness Index, Severity of illness, anaphylaxis, medicine, Humans, Aged, MESH: Anesthesia/adverse effects, MESH: Adolescent, MESH: Humans, MESH: Biomarkers/metabolism, business.industry, cardiac output, Reproducibility of Results, MESH: Adult, Carbon Dioxide, medicine.disease, MESH: Male, Confidence interval, respiratory tract diseases, Surgery, Clinical trial, hypocapnia, Anesthesiology and Pain Medicine, 030228 respiratory system, general, MESH: Drug Hypersensitivity/diagnosis, MESH: Drug Hypersensitivity/metabolism, business, MESH: Female, Biomarkers
Abstract

Background Prompt diagnosis of intra-anaesthetic acute hypersensitivity reactions (AHR) is challenging because of the possible absence and/or difficulty in detecting the usual clinical signs and because of the higher prevalence of alternative diagnoses. Delayed epinephrine administration during AHR, because of incorrect/delayed diagnosis, can be associated with poor prognosis. Low end-tidal CO2 (etCO2) is known to be linked to low cardiac output. Yet, its clinical utility during suspected intra-anaesthetic AHR is not well documented. Methods Clinical data from the 86 patients of the Neutrophil Activation in Systemic Anaphylaxis (NASA) multicentre study were analysed. Consenting patients with clinical signs consistent with intra-anaesthetic AHR to a neuromuscular blocking agent were included. Severe AHR was defined as a Grade 3–4 of the Ring and Messmer classification. Causes of AHR were explored following recommended guidelines. Results Among the 86 patients, 50% had severe AHR and 69% had a confirmed/suspected IgE-mediated event. Occurrence and minimum values of arterial hypotension, hypocapnia and hypoxaemia increased significantly with the severity of AHR. Low etCO2 was the only factor able to distinguish mild [median 3.5 (3.2;3.9) kPa] from severe AHR [median 2.4 (1.6;3.0) kPa], without overlap in inter-quartile range values, with an area under the receiver operator characteristic curve of 0.92 [95% confidence interval: 0.79–1.00]. Among the 41% of patients who received epinephrine, only half received it as first-line therapy despite international guidelines. Conclusions An etCO2 value below 2.6 kPa (20 mm Hg) could be useful for prompt diagnosis of severe intra-anaesthetic AHR, and could facilitate early treatment with titrated doses of epinephrine. Clinical trial registration NCT01637220.

Published
2017

14. CD32A-expressing platelets determine the severity of experimental anaphylaxis

Author

Beutier, Héloïse, Hechler, Béatrice, Godon, Ophélie, Wang, Yu, Gillis, Caitlin M., de Chaisemartin, Luc, Gouel-Chéron, Aurélie, Magnenat, Stéphanie, Macdonald, Lynn, Murphy, Andrew, Chollet-Martin, Sylvie, Longrois, Dan, Gachet, Christian, Bruhns, Pierre, Jönsson, Friederike, Anticorps en thérapie et pathologie - Antibodies in Therapy and Pathology, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Sorbonne Université - Faculté de Médecine (SU FM), Sorbonne Université (SU), Biologie et Pharmacologie des Plaquettes sanguines : hémostase, thrombose, transfusion (BPP), Université de Strasbourg (UNISTRA)-EFS-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Diderot - Paris 7 (UPD7), Laboratoire d'Immunologie 'Autoimmunité et Hypersensibilités' [AP-HP Hôpital Bichat, Paris], AP-HP - Hôpital Bichat - Claude Bernard [Paris], Cytokines, chimiokines et immunopathologie, Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM), Département d'Anesthésie Réanimation [CHU Bichat-Claude-Bernard], Regeneron Pharmaceuticals [Tarrytown], Physiopathologie et Epidémiologie des Maladies Respiratoires (PHERE (UMR_S_1152 / U1152)), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), We are thankful to our colleagues F. Abdallah, B. Iannascoli, and O. Richard-Le Goff at Institut Pasteur (Paris) for technical help. We are thankful to our colleagues for their gifts: M. P. Reilly and S. McKenzie (Jefferson Medical College, Philadelphia, PA) for FCGR2A transgenic mice and LFB Biomédicaments (Les Ulis, France) for human albumin and fibrinogen. Funding: This work was supported by the European Research Council (ERC)–Seventh Framework Program (ERC-2013-CoG 616050), by a Jeunes Chercheuses/Jeunes Chercheurs grant from the Agence National de la Recherche (ANR-16-CE15-0012-01), the Institut Pasteur, INSERM, the Société Française d’Allergologie (Soutien de la Recherche en Allergologie), and the Etablissement Français du Sang. H.B. was supported by a fellowship from the Université Pierre et Marie Curie. C.M.G. was supported partly by a stipend from the Pasteur-Paris University (PPU) International PhD program, by the Institut Carnot Pasteur Maladies Infectieuses, and partly by the Balsan company. Y.W. is part of the PPU International PhD Program that received funding from the European Union’s Horizon 2020 research and innovation program under the Marie Sklodowska-Curie grant agreement no. 665807 and from the Labex Milieu Intérieur, Institut Pasteur. A.G.-C. benefited from a stipend provided by Assistance Publique–Hôpitaux de Paris (Paris, France) and by the Institut Pasteur (Paris, France) (Postes d’accueil pour Praticiens Hospitaliers) and from a grant provided by INSERM, SFAR (Société Francaise d’Anesthésie et de Reanimation), and SRLF (Société de Réanimation de Langue Francaise) through the 'Bourse de Recherche du Comité d’interface INSERM-SFAR-SRLF 2012'. F.J. is an employee of CNRS., NASA study group : Vanessa Granger (UF Auto-immunité et Hypersensibilités, Hôpital Bichat, APHP, Paris, France, UMR996 - Inflammation, Chemokines et Immunopathology -, INSERM, Université Paris-Sud, Université Paris-Saclay, Châtenay-Malabry, France), Philippe Montravers (Département d’anesthésie-réanimation, Hôpital Bichat, AP-HP, Paris, France), Michel Aubier & Caroline Sauvan (Service de pneumologie et d’allergologie, Hôpital Bichat, AP-HP, Paris, France), Marc Fischler & Julie Bresson (Département d’anesthésie-réanimation, Hôpital Foch, Suresnes, France), Catherine Paugam-Burtz & Skander Necib (Département d’anesthésie-réanimation, Hôpital Beaujon, AP-HP, Clichy, France), Alexandre Mebazaa & Matthieu Le Dorze (Département d’anesthésie-réanimation, Hôpital Lariboisière, AP-HP, Paris, France), Laurent Jacob & Carole Chahine (Département d’anesthésie-réanimation, Hôpital Saint Louis, AP-HP, Paris, France), Hawa Keita-Meyer & Valentina Faitot (Département d’anesthésie-réanimation, Hôpital Louis Mourier, AP-HP, Colombes, France), Olivier Langeron & Sabrine Roche (Département d’anesthésie-réanimation, Hôpital Pitié Salpêtrière, AP-HP, Paris, France), Bernard Cholley & Jean Manz (Département d’anesthésie-réanimation, Hôpital Européen Georges Pompidou, AP-HP, Paris, France)., ANR-16-CE15-0012,PlanA,Rôle des plaquettes et leurs interactions dans les réactions anaphylactiques(2016), European Project: 616050,EC:FP7:ERC,ERC-2013-CoG,MYELOSHOCK(2014), European Project: 665807,H2020,H2020-MSCA-COFUND-2014,PASTEURDOC(2015), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Sud - Paris 11 (UP11), and Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
[SDV.IMM]Life Sciences [q-bio]/Immunology, [SDV.IMM.ALL]Life Sciences [q-bio]/Immunology/Allergology
Abstract

International audience; Platelets are key regulators of vascular integrity; however, their role in anaphylaxis, a life-threatening systemic allergic reaction characterized by the loss of vascular integrity and vascular leakage, remains unknown. Anaphylaxis is a consequence of inappropriate cellular responses triggered by antibodies to generally harmless antigens, resulting in a massive mediator release and rapidly occurring organ dysfunction. Human platelets express receptors for immunoglobulin G (IgG) antibodies and can release potent mediators, yet their contribution to anaphylaxis has not been previously addressed in mouse models, probably because mice do not express IgG receptors on platelets. We investigated the contribution of platelets to IgG-dependent anaphylaxis in human IgG receptor-expressing mouse models and a cohort of patients suffering from drug-induced anaphylaxis. Platelet counts dropped immediately and markedly upon anaphylaxis induction only when they expressed the human IgG receptor FcγRIIA/CD32A. Platelet depletion attenuated anaphylaxis, whereas thrombocythemia substantially worsened its severity. FcγRIIA-expressing platelets were directly activated by IgG immune complexes in vivo and were sufficient to restore susceptibility to anaphylaxis in resistant mice. Serotonin released by activated platelets contributed to anaphylaxis severity. Data from a cohort of patients suffering from drug-induced anaphylaxis indicated that platelet activation was associated with anaphylaxis severity and was accompanied by a reduction in circulating platelet numbers. Our findings identify platelets as critical players in IgG-dependent anaphylaxis and provide a rationale for the design of platelet-targeting strategies to attenuate the severity of anaphylactic reactions.

Published
2018

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